Cervical Neoplasia-Cyto-Histological Correlation (Bethesda ...
Cervical intra epithelial neoplasia
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Transcript of Cervical intra epithelial neoplasia
Aboubakr Elnashar Benha university, Egypt
https://www.facebook.com/groups/227744884091351/
2. PREMALIGNANT STAGE
Cervical intraepithelial neoplasia (CIN): includes
Dysplasia & CIS
CIN 1 = Mild D.
CIN 2= Moderate D.
CIN 3= Severe D or CIS.
Aboubakr Elnashar
CIN I CIN II
CINIII Aboubakr Elnashar
Squamous intraepithelial lesion (SIL): includes HPV
& CIN.
Low grade SIL= CIN 1 or HPV.
High grade SIL= CIN 2 or 3
Aboubakr Elnashar
Aboubakr Elnashar
HPV types
Oncogenic potential HPV TYPES
LOW 6, 11,14,43,44
INTERMEDIATE 31,33,35,51,52,
HIGH 16,18, 45, 56
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13 high-risk HPV
16, 18,
31, 33, 35, 39
45,
51, 52, 56, 58, 59,
68.
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Transition time of CIN
Stages Mean years
Normal to CIN 1-2 1.62
Normal to CIN 2-3 2.2
Normal to CIN 3 4.51
Clinical picture
Symptoms:
No symptoms: majority of cases
Postcoital bleeding
Vaginal spotting
Abnormal vaginal discharge
Suggestive findings
Clinically suspicious cervix
II. METHODS OF
CERVICAL CANCER
SCREENING A. Cytological
1. Conventional Pap. Smear
2. Liquid-based monolayers: LBC
3. Automated cytological screening
B. HPV testing
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C. Visual
1. Visual inspection of the cervix
a. Visual inspection with acetic acid (VIA)
b. Visual inspection with acetic acid and magnification (VIAM)
c. Visual inspection with Lugol’s Iodine (VILI)
2. Colposcopy.
3. Gynocular
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A. CYTOLOGY
1. Conventional Pap test used for ≥50 y all across the globe.
widely used for in most developed countries
Meets all the requirements for mass screening:.
Fairly tolerated by patients
Easy to administer
Reasonable sensitivity & specificity.
Detection of endocervical lesions.
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Precautions:
No sexual intercourse, vaginal douche, medication
No lubrication, powder, pelvic examination , acetic acid
Instruments & materials:
Speculum
Spatula:
Cytobrush or cotton tipped swab for the endocervical canal
Ayre s spatula for the ectocervix
Fixative
Jar
Slide
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Steps:
Taking the sample: from the ectocervix and endocervix, either with a spatula or brush
Smearing: circular motion
Fixation: Ethyl alcohol, Coating spray
Staining:
Examination under
a microscope by specially
trained technologists and
doctors.
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Aboubakr Elnashar
Aboubakr Elnashar
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CINIII
CINIII
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Limitations
Moderate to low sensitivity: High rate of false-negative test results 20-40%
Women must be screened frequently
Rater dependent
Requires:
Complex infrastructure: Complex laboratory test
Trained cytologist
Multiple visits
Continuous monitoring to maintain high-quality results
Results are not immediately available
Less accurate among post-menopausal women
Impossible to locate the lesion.
Usually available only in large cities in many
countries
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Aboubakr Elnashar
Frequency of Pap test
CDC recommendation
21 to 29y: Pap test /3 y.
30 to 65y: Pap test /3 y or
Pap test plus HPV test/5 y.
2. Liquid-based monolayers
(ThinPrep, CytoRich)
Steps:
•Cells are collected using a brush instead of a spatula.
•Head of the brush is vigorously shaken or broken off into a small pot of liquid containing preservative solution.
•The sample is filtered or centrifuged to remove excess blood and debris.
•The cells are then transferred to the slide in a “mono” layer.
•Staining.
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Advantages:
•It removes most mucus, protein& fresh blood cells,
•distributes the cells uniformly
•improves fixation
•maintains diagnostic clusters
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LBC Vs Conventional Pap
More expensive
Repeat smear rates: 1 to 2% Vs 9%
Less false negative rate
No difference in the relative sensitivity.
No difference in the relative specificity, when H
and L- GSIL were considered as cutoff.
Better in predicting CIN
It is the preferred tool for cervical cytology
screening
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Aboubakr Elnashar
3. Automated Pap smears
To reduce errors by using computerized analysis to evaluate Pap smear slides.
1. Autocyte
•Composed of an algorithmic & neural network scanner
•Scans the slides & records images of 128 of the most abnormal fields found on the slide, with the most significant abnormality found in the center.
•It reduces costs & shortens screening time.
•Detects 97.2% of the abnormal tests (Koss et al,1994).
Aboubakr Elnashar
Aboubakr Elnashar
2. AutoPap.
The material on the slide is reviewed and scored based on an algorithm, as to the likelihood of an abnormality being present.
Typically, it does not show the cytotechnologist which of the cells are likely to be abnormal.
Variety of visual characteristics, such as shape and optical density of the cells, are included in the algorithm.
•It reviews all normal & satisfactory smears
•As a primary screener, it removes 30 % of slides from the workload
•97% sensitivity (Lee et al, 1997) Aboubakr Elnashar
B. HPV TESTING
Role of HPV as a causative agent of cervical
cancer has been well established.
However, most HPV infections in young women regress rapidly, without causing clinically significant disease. infection is a marker of sexual activity than of cervical cancer risk.
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Hybrid Capture II kit (HC II, Qiagen Inc., USA)
Approved by FDA : frequently used. The sample is collected similar to Pap, with a
cervical swab from TZ and placed into transport
medium.
Detects whether a person is infected with one or
more of the 13 high-risk HPV viral types (types16,
18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68).
It is used as
Routine screening test above 30 to 35 y
To evaluate equivocal Pap test. ASCUS or LGSIL:
Oncogenic HPV: Colposcopy.
≥35 y: HPV testing/5 years & if +ve: Pap smear
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•Negative predictive value: very high
•HPV testing could augment but not replace cytological screening Sensitivity for detecting CIN 2–3 lesions: 45.7 to
80.9%
Specificity: 91.7 to 94.6%.
HPV testing (Qiagen HCII) most objective and reproducible of all cervical screening tests less demanding in terms of training and quality assurance.
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HPV testing
sophisticated lab
unaffordable ($20 to $30/test) in less-developed
countries.
HPV DNA- PCR testing (HPV typing): [Current technique (HC2) Hybrid Capture 2] Isolated HPV types could be detected.
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Care HPV test (Qiagen Inc. USA)
Detect several types of HPV rapidly (within 3 h)
No need:
specially trained personnel or
sophisticated lab.
{simplicity and rapid completion}: screening and
clinical follow-up to be completed on the same day.
low cost: $8/test
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C. VISUAL
1. Visual examination of cervix
a. Visual inspection after application of acetic acid
(VIA)
b. VIA with magnification (VIAM)
c. Visual inspection after application of Lugol’s iodine
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Effects of acetic acid:
Coagulates the proteins of the nucleus &
cytoplasm: protein opaque & white.
Dehydrates the cells: cytoplasmic volume is
reduced & the reflection is increased.
Duration:
appears after 20 seconds
disappears after 2 minutes.
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Category Clinical Findings
Negative
No acetowhite lesions or
faint acetowhite lesions;
polyp,
cervicitis, inflammation,
Nabothian cysts.
Positive Sharp, distinct, well-defined,
dense (opaque/dull or oyster white) acetowhite with
or without raised margins touching SCJ;
leukoplakia and
warts.
Suspicious
for cancer
ulcerative, cauliflower-like growth or
ulcer; oozing and/or bleeding on touch. Aboubakr Elnashar
2 . Visual inspection with acetic acid (VIA)
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Normal NAAT
Positive
Suspicious for cancer
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VIA Performance:
Source: Adapted from Gaffikin, 2003
Sensitivity Specificity
Pap 47-62 60-95
VIA 76-84 79-83
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Aboubakr Elnashar
3. Visual Inspection with Acetic Acid Using
Magnification (VIAM) Gynoscopy = Aided VIA
visualization of cervix after application of aa using low power magnification
(2.5x to 4x)
Inexpensive, easy to use portable system, which can be used to screen cervical cancer in developing countries.
Sensitivity: 80%
Specificity: 95% compared to Pap smear
Magnascope (4X)
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4. Visual inspection after application of Lugol’s
iodine
Test performance:
(Sankaranarayanan et al., 2008).
Specificity Sensitivity
85.5 76.8 VIA
85.4 91.7 VILI
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Categories for VILI test results:
Category Clinical Findings
Negative Squamous epithelium turns brown
Columnar epithelium does not change
color; or
Irregular, partial or non-iodine uptake
areas.
Positive Well-defined, bright yellow iodine non-
uptake areas touching SCJ or close to the
os if SCJ is not seen.
Suspicious
for cancer
Ulcerative, cauliflower- like growth or
Ulcer; oozing and/or bleeding on touch.
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VILI: test-positive
Well-defined
bright yellow iodine non-uptake areas
touching the SCJ
2. Colposcopy
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Colposcope :
Microscope
Low-power, stereoscopic, binocular field
Powerful light source
Moving system
The most common indication:
positive screening tests: positive cytology
positive on VIA.
Biopsies from suspicious areas
Endocervical curettage:
when the colposcopy is unsatisfactory, i.e. scj
cannot be visualized.
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Aboubakr Elnashar
Swede score
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Swede score of 4 and above:
Punch biopsies of the cervix
Swede score 6 and above:
immediate tt
with cold coagulation under visualisation with the Gynocular and local anaesthesia. patients not suitable for cold coagulation or with biopsies revealing microinvasive cervical disease or worse: appropriate diagnostic workup and management protocol.
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Aboubakr Elnashar
3. Gynocular Mini colposcope portable colposcope
Easy to use: Handheld or used with a tripod
Pocket-size battery: Battery operated (2 h of working time/charge)
Provide gold-standard examination: Red-free/green filter mode
Capture digital images
Take videos
low-resource countries.
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Aboubakr Elnashar
charger and mounting clip
for camera tripod.
lens, green filter,and warm
white LED illumination.
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Aboubakr Elnashar
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III. SCREENING IN DEVELOPING COUNTRIES
Difference between developing & developed countries
I. Higher incidence: 80%
II. Higher mortality: 90%
III. Different risk factors
IV. Poor financial, human & technical resources
V. Inadequate follow up
Screening used in the developed world is inappropriate in developing countries (Singer,1995) Aboubakr Elnashar
Alliance for Cervical Cancer Prevention
2009 1. optimal age-group for cervical cancer screening
to achieve the greatest public health impact is 30–39-y-olds.
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2. Cytology-based screening programs using Pap smears have been shown to be effective in
developed countries, sustaining high-quality
cytology- based programs is difficult in low-resource
settings.
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3. The most efficient and effective strategy
VIA or
HPVDNA testing and then to treat using
cryotherapy.
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TREATMENT
I. Ablative (destructive)
1. Cryotherapy
2. Cold coagulation
3. Laser vaporization
II. Excisional
A . LETZ B. Conization:
1. LEEP
2. Cold knife (CKC)
3. Laser
III. Hysterectomy
CIN: WHO Recommendation 2014. CIN 1:
(i) immediate tt
(ii) follow the woman and then tt if the lesion is
persistent or progressive after 18 to 24 months.
CIN 2 and CIN 3:
Cryotherapy or LEEP.
AIS (adenocarcinoma in situ)
CKC
Strategy Three visits strategy
one for screening
one for colposcopy,
one for treatment: poor compliance, especially
among rural women.
Single visit: see-and-treat strategy
satisfactory results
no significant extra morbidity [Emam et al, 2009].
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See & treat (Single visit diagnosis & tt)
•It means
(Cryo therapy, cold coagulator or LEEP) at first visit to women with (VIA or colposcopic) findings suggestive of SIL.
•Advantages:
False negative histology is low (4.7% )
Reduce waiting lists & anxiety
•Disadvantages:
Over tt of insignificant lesions
•It should be limited to HGSIL (Pastner,1994)
III. Hysterectomy
Indications
1. Other gynecological conditions:
.fibroid, prolapse, endometriosis, PID .
2. Refuse all other forms of therapy
3.SIL at limits of conization specimen
4. Poor compliance with follow-up
Sterilization is not an indication
Treatment of CIN during pregnancy
•Abnormal cytology Colposcopy
•Colposcopically directed punch biopsy or
small loop biopsy
•Knife or LLE cone: rarely indicated
•Colposcopy/ 3 m to ensure that the lesion is not
progressing
•CIN 3: treatment after delivery
Prof. Aboubakr Elnashar Benha University Hospital, EGYPT
E-mail: [email protected]